Tobacco use remains the single most preventable cause of premature deaths and cancer.1 Building on more than a decade of clinical and research experience in treating tobacco-dependence, we propose to address this problem with a new academic-small computer game business partnership that will develop a novel e-health tobacco cessation and relapse prevention product. Smoking relapse following a quit attempt remains a significant public health concern with high costs in quality-adjusted life years. A growing body of evidence suggests that continued practice, or behavioral rehearsal, can help smokers effectively manage smoking cues, and also that cues to smoke can be triggered virtually via interaction with a computer.2 Thus, we propose to create a 3D game intervention that aims to help smokers rehearse effective strategies and improve self- efficacy for managing smoking triggers. Given our preliminary work with this concept, our combined expertise, and the commercialization potential of this concept, we are pursuing a Fast Track submission. In Phase I we plan to transform our coping skills simulation developed in the virtual world Second Life to an accessible, structured gaming environment with elements essential for a full-fledged interactive game designed to promote tobacco cessation. Using a systematic feedback protocol, we will refine the game's usability, relevance and utility using patient volunteers recruited from the Memorial Sloan-Kettering Tobacco Cessation Program and behavioral science researchers with expertise in treating tobacco dependence. In Phase II we will incorporate alpha testing data and complete development of the coping skills game, including the 3D environment and game avatars, game design and scripts for coping skills, feedback and rewards for patients, and data collection capabilities. Then, using a randomized trial design conducted at Memorial Sloan-Kettering Cancer Center, we will test the game's potential to increase coping self-efficacy and decrease relapse to smoking among hospitalized cancer patients. Although rates of cessation among patients newly diagnosed with tobacco-related cancers are typically high, many continue to smoke or resume smoking shortly after discharge from the smoke- free, hospital environment.3-5 Despite often reporting high motivation to quit and serious consequences of continued smoking, cancer patients are at high risk for smoking relapse following hospitalization and an ideal population with which to test the potential of our game. We will randomize 190 patients using a two-group design (Usual Care + Smoking Cues Coping Skills Game vs. Usual Care Only) and gather self-efficacy and tobacco use data at 1, 3, and 6 months following hospitalization. The proposed study has the potential for high impact if our novel coping skills game shows efficacy for enhancing the treatment of tobacco dependence. This concept is highly marketable to a broad target audience of hospitalized smokers and may offer numerous benefits as an adjunct to current cessation interventions.